tbuckley/cabot-search huggingface dataset:
AB1441 LEARNING NEEDS ASSESSMENT FOR PATIENTS WITH CANCER AND A PRE-EXISTING AUTOIMMUNE DISEASE WHO ARE CANDIDATES TO RECEIVE IMMUNE CHECKPOINT INHIBITORS
Authors: M. A. Lopez-Olivo, J. I. Ruiz, G. F. Duhon, M. Altan, H. Tawbi, A. Diab, C. Bingham, C. Calabrese, R. Volk, M. Suarez-Almazor
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with autoimmune disorders and cancer are at risk of developing immune-related adverse events (irAEs) and increasing flares of their underlying disease with immune checkpoint inhibitors (ICI) and harms and benefits must be weighed. Objectives We conducted an assessment of learning needs. Methods We interviewed 19 patients who had received an ICI and 20 physicians who provide care for these patients. We asked what do cancer patients with pre-existing autoimmune diseases need to know in order to make an informed decision about whether to receive an ICI. Results Fifty-three percent of the patients were female, median age was 62.9 (±10.9). They had rheumatoid arthritis (47.4%), psoriasis (26.3%), Crohn’s disease (10.5%), ankylosing spondylitis (5.3%), systemic lupus erythematosus (5.3%), or ulcerative colitis (5.3%). Half of the patients (52.6%) had a demonstrable disease activity of the autoimmune disease at the time of making the decision on whether to start ICI. Most (84%) of the patients had melanoma, and at the time of the interview 68.4% had completed or discontinued the ICI. Physicians were melanoma oncologists (30%), thoracic-head &amp; neck medical oncologists (25%), rheumatologists (20%), gastroenterologists (10%), and dermatologists (15%) who treat patients with irAEs. Sixty percent were female. Key points mentioned by patients and physicians included information on probability of irAEs and flares of the autoimmune condition with discussion about severity, benefits of ICI, ICI mechanism of action in the context of the autoimmune disease, and management for flare-ups. Key topics raised only by patients included possible reasons for stopping or modifying treatment (for cancer or autoimmune disease), when to contact the provider, possibility of autoimmune disease progression or organ damage, sharing information with other providers, and lifestyle changes that can be done to help. Conclusion Although patients and physicians listed common learning points, patients also considered specific needs to increase their self-care. The information derived from this study will be used to develop a decision support tool. Disclosure of Interests None declared
AB0031 DEEP IMMUNE PHENOTYPING OF SLE AND RA BY MACHINE LEARNING
Authors: B. Prietl, J. Vera-Ramos, L. Herbsthofer, V. Pfeifer, P. Lopez-Garcia, H. P. Brezinsek, T. R. Pieber, M. Stradner
Journal: Annals of the Rheumatic Diseases (2022)

Background Breakdown of self-tolerance is an important common mechanism in autoimmunity. Despite considerable clinical heterogeneity, many autoimmune diseases exhibit common immunological mechanisms leading to a breakdown of self-tolerance. Identification of unique and similar patterns across different autoimmune disease may help to understand their pathophysiology behind. Objectives Establishing workflows for the multi-parameter deep immune phenotyping of T- and B-cells by unsupervised machine learning (ML) methods for feature extraction, cluster analysis and anomaly detection. Methods We use machine learning to identify common patterns and dissimilarities between type 1 diabetes (T1D, n=69), rheumatoid arthritis (RA, n=63), systemic lupus erythematosus (SLE, n=38) and healthy controls (n=69) samples based on multi-plex immune phenotyping. PBMCs were isolated from patients with T1D, RA, SLE, and controls. A flow cytometry-based approach was applied, and a traditional analysis was compared to a ML method implemented in R [1] and based on self-organizing maps (Figure 1). Our pipeline includes unsupervised pre-gating, normalization, FlowSOM clustering [2], and a statistical model (GLMM), to check for significant differential abundances of cell populations among the autoimmune conditions. Figure 1. Results After applying our automated workflow to one T cell panel we could identify 14 cell clusters present in all the samples. The GLMM test revealed a cluster with a significant difference (p=0.035) and a trending one (p=0.059) on the abundance across the different diseases. In particular, CD4 pos T cells expressing high IL-7 receptor (CD127) levels and median amounts of CD15s but low CD25, CD161 and FoxP3 are increased in T1D whereas CD4 + CD25 ++ CD15s + FoxP3 low CD161 low CD45RA - cells are increased in SLE. Conclusion This unbiased, unsupervised ML workflow was able to identify canonical and novel clusters of T cells that are similar in RA, SLE and T1D. Additionally, a novel memory T cell population expressing CD15s was shown. This unsupervised analysis approach for large datasets enables the discovery of new immune cell populations complementing traditional workflows. References [1]Ellis B, Haaland P, Hahne F, Le Meur N, Gopalakrishnan N, Spidlen J, Jiang M, Finak G (2021). flowCore: flowCore: Basic structures for flow cytometry data. R package version 2.6.0. [2]Van Gassen S, Callebaut B, Van Helden MJ, Lambrecht BN, Demeester P, Dhaene T, Saeys Y. FlowSOM: Using self-organizing maps for visualization and interpretation of cytometry data. Cytometry Part A. 2015 Jul;87(7):636-45. Acknowledgements This work was funded by a grant from JDRF, LRA and NMSS (grant key: 2-SRA-2021-1043-S-B) and the Austrian Federal Government within the COMET K1 Centre Program, Land Steiermark and Land Wien Disclosure of Interests None declared
POS1525-HPR BODY SELF-ESTEEM AND SEXUAL FUNCTION IN IMMUNE-MEDIATED INFLAMMATORY DISEASES
Authors: C. Heredia Coca, L. Castiblanco, C. Aragón-Benedí, P. Oliver-Forniés, J. M. Martín Martín, L. Leon Mateos
Journal: Annals of the Rheumatic Diseases (2022)

Background The Immune-Mediated Inflammatory Diseases (IMID) are a group of pathologies that have in common an altered immune system causing a chronic inflammatory process. IMIDs usually have a significant impairment of quality of life, including affective and sexual components. Objectives To describe body self-esteem and sexual function in patients with IMIDs. Secondly, to compare outcomes between rheumatic IMIDs patients and those with other IMIDs. Methods A cross-sectional comparative study was performed including 38 patients with rheumatic IMIDs (including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis), compared to 34 patients with other IMIDs (psoriasis and inflammatory bowel disease). All participants fulfilled the Body Self-Esteem Scale (EAC) to measure body self-esteem, and also the International Index of Erectile Function (IIEF-15) for men, and the Female Sexual Function Index (FSFI) for women. Results The prevalence of sexual dysfunction in our study was 66.7%. A trend of greater impairment in sexual function was observed in women. There was a higher percentage of sexual dysfunction in the gastrointestinal IMIDs group (79.2%), compared to rheumatic diseases (60.5%) and dermatological diseases (60%), but no significant differences were found regarding the sexual dysfunction between groups (χ 2 = 2.53, p = 0.28). Our results showed a significant inverse relationship between body self-esteem and sexual function (p = 0.012), i.e., the lower the body self-esteem, the higher the probability of presenting sexual dysfunction. Conclusion Sexual function was impaired in all IMIDs. Body self-esteem problems were an important factor of sexual dysfunction in IMIDs. Healthcare professionals should be aware of these potential problems, promote self-care, and address sexual issues. References [1]Peris M, Maganto C, Garaigordobil M. Body Self-Esteem Scale: psychometric reliability and validity data. Rev. Psicol. Clín. Niños Adolesc. 2016; 3(2):51–8. [2]Rosen, R., Riley, A., Wagner, G., Osterloh, I., Kirkpatrick, J., y Mishra, A. (1997). The international index of erectile function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology, 49, 822-830. [3]Sánchez-Sánchez F, Ferrer-Casanova C, Ponce-Buj B, et al. Design and validation of the second edition of the Women’s Sexual Function Questionnaire, FSM-2. Medicina de Familia SEMERGEN. 2020;46(5):324-330. Disclosure of Interests None declared
AB0440 USE OF BELIMUMAB IN CLINICAL PRACTICE. CLINICAL AND SEROLOGICAL EFFECTIVENESS AND CORTICOSTEROID-SPARING ACTIVITY
Authors: S. Vela-Bernal, E. Fuertes, P. Albiol, I. de la Morena, C. Bea, A. I. de Gracia, A. de Castro, L. Navarro, M. J. Forner
Journal: Annals of the Rheumatic Diseases (2022)

Background Since 2011, the use of Belimumab for the treatment of Systemic Lupus Erythematosus (SLE) has demonstrated efficacy and safety in several randomised clinical trials. However, strict inclusion criteria may restrict those results limiting the interpretation of these results to routine clinical practice populations. Objectives The aim of this study was to analyse the profile of patients using Belimumab as well as the clinical, serological and corticosteroid-sparing outcomes that may result from it use. Methods Retrospective cohort study including patients diagnosed with SLE and treated with Belimumab. Epidemiological, clinical and analytical data were collected at 6, 12 and 24 months before and after starting treatment with Belimumab. To assess effectiveness, the SELENA-SLEDAI, SLICC, clinical changes, concomitant treatments, corticosteroid dose and ds-DNA and C3-C4 levels were used. Safety was evaluated by assessing the need and cause for discontinuation of Belimumab. Results Thirty-one patients were included, mostly 28 (90.32%) women, with a mean age of 48.55 ± 1.95 years and a mean time of disease progression since diagnosis of 16.13 ± 1.77 years. The most prevalent affection before initiation of Belimumab were joint (83.87%), systemic (58.06%), skin (29.03%) and nephropathy (22.58%). The mean SELENA-SLEDAI score before Belimumab was 5.32 ± 0.46; 64.5% had elevated anti-dsDNA, 48.39% and 54.84% had low C3 and C4 levels, respectively. Before starting Belimumab, the most used treatments were both antimalarials (72.4%) and corticosteroids (80.6%). The main reason for starting Belimumab was the ineffectiveness of previous treatments (67.7%). The vast majority of patients were treated subcutaneously (90.3%) and there were no major adverse events leading to drug withdrawal, with a median duration of use of 19.3 months (IQR: 9.75-35.55). Conclusion After starting Belimumab, a decrease in the SELENA-SLEDAI activity scale, an increase in C3 and C4 levels, and a significant decrease in anti-dsDNA levels at 6 months were observed. At 12 and 24 months, continuity of this trend was observed, although statistical significance was not reached. As concerns corticosteroids, we observed a decrease in steroid use below 7.5mg/day and even 5mg/day after the introduction of Belimumab avoiding the undesirable effects of prolonged steroid use. Table 1. BEFORE BELIMUMAB (n=31) 6 MONTHS (n=28) 12 MONTHS (n=22) 24 MONTHS (n=9) ESLEDAI x̄ (SD) 5,32 (0,46) 2,28 (0,44) 2,90 (0,72) 3,44 (1,39) P&lt;0,001 P&lt;0,005 p&gt;0,05 High dsDNA - n (%) 18 (58,06) 14 (61,29) 14 (45,16) 4 (12,9) P&lt;0,001 P=0,036 P=0,7 Low C3 (&lt;90mg/dl) - n (%) 15 (48,39) 11 (35,48) 9 (29,03) 3 (9,68) P=0,006 P=0,193 P=0,06 Low C4 (&lt;16mg/dl) - n (%) 17 (54,84) 14 (45,16) 11 (35,48) 5 (16,13) P&lt;0,001 P=0,003 P=0,217) Figure 1. Disclosure of Interests None declared
POS1283 THE COURSE OF NOVEL CORONAVIRUS DISEASE 2019 (COVID-19) IN PATIENTS WITH IgG4-RELATED DISEASE TREATED WITH RITUXIMAB
Authors: E. Sokol, A. Torgashina
Journal: Annals of the Rheumatic Diseases (2022)

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) raised many questions and concerns about the safety of different immunosuppressive agents in patients (pts) with rheumatic diseases during the pandemic. There is some data that anti-B-cell depletion strategies could lead to more severe disease course. Rituximab (RTM) is one of the most effective, safe and well tolerated agents in IgG4-related disease (IgG4-RD) treatment. Information about the course of COVID-19 in pts with IgG4-RD is lacking. Objectives To examine clinical course of COVID-19 in pts with IgG4-RD treated with anti-CD20 monoclonal antibody (RTM). Methods Single center observational study. We searched in our clinical base from 2019 to 2021 years for pts with IgG4-RD, treated with RTM within this period. Diagnosis of IgG4-RD was based on comprehensive diagnostic criteria (H. Umehara, 2011). COVID-19 infection was registered when PCR test results were positive. RTM was administered in two 1000 mg infusions 14 days apart for the 1 st course, then 500 mg every 6 months. We used mean ± standard deviation and median values ​​ with interquartile range of 25 - 75 percentile to characterize quantitative data. Results Fifteen pts, 6 women and 9 men, mean age 53.2 ± 12 years, receiving RTM monotherapy were included. The majority of patients (80%) had multiple organ involvement, mean number 2,3 (from 1 to 5): dacryadenitis – 11 pts, sialadenitis – 10 pts, AIP 1 – 4 pts, lung disease – 3 pts, sclerosing cholangiris – 2 pts, kidney disease – 2 pts, retroperitoneal fibrosis – 1 pt, aortitis – 1 pt, prostatitis – 1 pt. Median duration of IgG4-RD before COVID-19 onset was 48 [27;72] months, median duration of RTM treatment was 22 [11,5;30,5] months and median time from the last dose of RTM was 2 [1;4,5] months. Three pts had arterial hypertension or coronary heart disease anamnesis, 4 pts had asthma, 2 pts were overweight and 1 had class 3 obesity. No pts were vaccinated against SARS-CoV-2. Six patients (40%) required hospitalization and 4 of them received IL-6 inhibitors, only 1 required mechanical lung ventilation, 6 patients (40%) had only minor symptoms and didn’t require any specific treatment, glucocorticoids were administered to 8 patients. All patients, except one, were older than 50, but they didn’t have severe comorbidities. One patient, a 46 year-old man with a long anamnesis of IgG4-related dacryo- and sialadenitis, bronchial asthma, arterial hypertension class 3 and class 3 obesity, died. Due to small number of studied pts no statistical correlations could be established. Conclusion The proportion of hospitalized pts with IgG4-RD and RTM treatment was surprisingly high. The worst course was in patient with severe comorbidity. It appears that RTM can have negative impact on susceptibility to COVID-19 and its disease course. Disclosure of Interests None declared
AB1027 CLINICLAL EFFICACY OF SEQUENTIAL TREATMENT AFTER ROMOSOZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS FOR 18 MONTHS
Authors: Y. Kanayama
Journal: Annals of the Rheumatic Diseases (2022)

Background Romosozumab (ROMO), a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. And although it is a novel therapeutic agent for osteoporosis, which has shown high effects of increasing bone density and inhibiting fragile fracture in overseas clinical trials. However the clinical efficacy for rheumatoid arthritis complicated with osteoporosis (RA-OP) is unknown. Objectives To evaluate the clinical efficacy of ROMO for 12months and denosumab (DMB) 6months in patients with RA-OP for 18 months. Methods RA patients diagnosed according to the 2010 ACR/EULAR criteria. All patients met at least one of the following criteria were eligible; a bone mineral density T score of -2.5 or less at the lumber spine or total hip and either one or more moderate or severe vertebral fractures or two or more mild vertebral fractures. All patients were initiated ROMO from between April, 2019 and March, 2020. The total number of patients was 12 cases. The ROMO dose was 210mg at once every 1 months. After 12 months of ROMO, all cases were changed to DMB. In all cases native or activated vitamin D has been used. We reviewed the results for 12 months about the increase and decrease of bone mineral density (BMD) of lumbar spine(LS) and total hip(TH) by DEXA and bone turnover markers, intact n-terminal propeptide type I procollagen(PINP) and tartrate-resistant acid phopshatate form 5b(TRACP-5b). Results he gender was all female. The mean age was 72.8 ± 7.0; disease duration was 17.7 ± 16.5 years; the body mass index was 19.4 ± 3.1 and the FRAX was 36.0 ± 14.9. Clinical findings related to RA-OP at baseline were as follows; CRP 1.25 ± 1.75; DAS28-CRP 3.45 ± 0.99; HAQ 1.56 ± 0.99 and, bone turnover markers and bone mineral density at baseline were as follows; P1NP 62.4 ± 36.2; TRACP-5b 485 ± 252; LS-BMD and T-score 0.79 ± 0.14 g/cm 2 and -2.82 ± 0.99 and TH-BMD 0.55 ± 0.07 g/cm 2 and -3.14 ± 0.53 g/cm 2 . The rate of increased P1NP from baseline to 1, 3, 6, 12 and 18 months were each 116.3 ± 68.7% at 1 month, 135.0 ± 131.3% at 3 month, 126.1 ± 177.0% at 6 month, 83.7 ± 179.1% at 12 month and -45.1 ± 35.7% at 18 month and decreased TRAC-5b were -13.0 ± 91.4% at 1 month, 6.9 ± 38.8% at 3 month, 20.0 ± 63.4% at 6 month, 14.8 ± 64.5% at 12 month and -11.4 ± 95.9% at 18 month. The rate of increased LS-BMD from baseline to 6, 12 and 18 months were 10.8 ± 8.0%, 15.2 ± 9.5% and 18.9 ± 10.4% and TH-BMD were 4.1 ± 4.5%, 5.7 ± 6.3% and 8.4 ± 8.1% (Figure 1, 2). Conclusion Clinical efficacy of treatment with ROMO for 12months and DMB for 6months for RA-OP was extremely effective and has the high potential to be an important option in the treatment of RA-OP. Disclosure of Interests None declared
AB0331 REDUCED C-REACTIVE PROTEIN LEVEL AT HOSPITAL ADMISSION IN PATIENTS TREATED WITH TOCILIZUMAB IN COMPARISON WITH OTHER ADVANCED ANTIINFLAMMATORY TREATMENTS- AN ATTENTION MAY BE REQUIRED
Authors: M. Berman, S. Berliner, N. Bashouti, O. Elkayam, T. Ziv-Baran
Journal: Annals of the Rheumatic Diseases (2022)

Background C-reactive protein (CRP) is a marker of inflammation and infection. The main proinflammatory cytokine that leads to CRP gene expression is IL-6[1]. Different DMARDS may influence CRP levels due to their specific mechanisms of action and alter its usage as an important indicator of acute infection/inflammation Objectives The study aimed to compare CRP level between patients who were treated with Tocilizumab (TCZ), an il-6 receptor blocker, and other advanced anti-inflammatory treatments (AAIT), as well as with other admitted and non-admitted populations. Methods A cross-sectional study of all patients (≥18 years) hospitalized at tertiary medical center between 12/2009 and 02/2020 and treated before hospitalization with (AAIT). Data on background DMARDS treatment was collected and then categorized to one of the two following groups: tocilizumab treatment and other treatments. In further investigation, the other treatments groups were divided into 3 subgroups: anti-TNF subgroup which included Infliximab (IFX), Adalimumab (ADA), etanercept (ETN), Golimumab, and Certolizumab, JAK-inhibitor subgroup which included Tofacitinib and Baricitinib, and another subgroup which included Rituximab, Abatacept and Anakinra Only the first hospitalization of each patient was included. Women admitted to obstetrics department were excluded. Demographic data, first blood tests results, and comorbidities were collected. Results The study included 563 patients treated with AAIT (2.5% received TCZ). Patients treated with TCZ were older (median 75 vs. 50 years, p&lt;0.001), had higher Charlson score (median 5 vs. 1, p&lt;0.001) and more infectious diseases at admission (50% vs. 23.4%, p=0.05). Patients treated with TCZ had lower CRP levels (median 0.5 vs. 25mg/l, p&lt;0.001) and more common normal values (64.3% vs. 20.8%, p&lt;0.001) compared to patients treated with other AAIT. CRP level in patients treated TCZ (median 0.5mg/l) was lower than that of 58,548 patients admitted to the hospital between 2010-2020 (median 12.55mg/l, p&lt;0.001) and not statistically different from 140 non-admitted randomly selected individuals without acute disease (1.33 mg/l, p=0.294). Conclusion When compared to other anti-inflammatory drugs, tocilizumab is associated with lower CRP levels in individuals admitted to an acute care hospital. This finding must be considered by treating physician to avoid misinterpretation of CRP results. References [1]Zhang D, Sun M, Samols D, Kushner I. STAT3 participates in transcriptional activation of the C-reactive protein gene by interleukin-6. J Biol Chem. 1996;271(16):9503-9509. https://doi.org/10.1074/jbc.271.16.9503 Disclosure of Interests None declared
POS1144 INCREASED EXPRESSION OF RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS IN SARCOPENIC PATIENT SKELETAL MUSCLE
Authors: J. S. Hwang, J. Kim, H. S. Gong, G. H. Baek
Journal: Annals of the Rheumatic Diseases (2022)

Background Animal studies suggest that advanced glycation end-products (AGEs) and their interaction with receptor for AGEs (RAGE) are involved in sarcopenia, but their relationship in human skeletal muscles has yet to be elucidated. Objectives We aimed to determine whether RAGE expression in human skeletal muscle is associated with serum AGE levels and sarcopenia-related changes. Methods We reviewed 33 consecutive women (mean age, 65 years) with distal radius fracture who had consented to donate a sample of forearm flexor muscle for research purposes, which was taken during surgical fracture repair. The muscle RAGE expression was measured with immunohistochemistry staining and serum AGE levels using ELISA method. We compared RAGE expression and AGE levels in patients with and without sarcopenia. We also correlated RAGE expression with such clinical parameters as age, body mass index, bone mineral density (BMD), as well as sarcopenia-related changes, including grip strength, appendicular skeletal muscle mass, and muscle cross-sectional area (CSA) ratios. Results Twelve patients (36%) were diagnosed with sarcopenia according to the Asian Working Group for Sarcopenia. They had a significantly higher RAGE expression ( p = 0.044) and AGE level ( p &lt; 0.001) than those without sarcopenia. The RAGE expression correlated significantly with a high serum AGE level ( r = 0.510, p = 0.011) and correlated inversely with a muscle CSA ratio ( r = -0.696, p &lt; 0.001). Conclusion This study shows that RAGE expression increases in sarcopenic patient skeletal muscles. This expression also correlates positively with serum AGE levels and inversely with muscle CSA ratios. Further studies are necessary to determine whether targeting RAGEs can be a therapeutic option for sarcopenia. References [1]Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001; 44: 129-46. [2]Tabara Y, Ikezoe T, Yamanaka M et al. Advanced glycation end product accumulation is associated with low skeletal mass, weak muscle strength, and reduced bone density: the Nagahama study. J Gerontol A Biol Sci Med Sci. 2019; 74: 1446-53. [3]Riuzzi F, Sorci G, Sagheddu R, Chiappalupi S, Salvadori L, Donato R. RAGE in the pathophysiology of skeletal muscle. J Cachexia Sarcopenia Muscle. 2018; 9: 1213-34. Figure 1. Skeletal muscle tissue (x 7.0) obtained from (a) a 76-year-old female with receptor for advanced glycation end-products (RAGE) expression scoring 14, and (b) a 75-year-old female with RAGE expression scoring 50. Disparity between the percentage of fibers with signal intensity of 1+ (arrow) and those with signal intensity of 2+ (arrowhead) is obvious. Difference in the diameter and homogeneity of the muscle fibers imply the role of RAGE hyperexpression in sarcopenia. Disclosure of Interests None declared